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Suvarna Y and Abdul Rahaman SK. /Asian Journal of Research in Chemistry and Pharmaceutical Sciences. 7(1), 2019, 293-304.
Available online: www.uptodateresearchpublication.com January – March 293
Review Article ISSN: 2349 – 7106
PHARMACOTHERAPEUTIC PROPERTIES OF BLACK PEPPER: A SYSTEMATIC
REVIEW
Y. Suvarna*
1
and SK. Abdul Rahaman
1
1*
Department of Pharmaceutical Analysis, Nirmala College of Pharmacy, Mangalagiri, Andhra Pradesh, India.
.
INTRODUCTON
A natural product is a chemical
compound or substance produced by a living
organism that is, found in nature. Natural products
can also be synthesized by chemical methods and
have plays a major role in the development of the
field of organic chemistry by providing challenging
synthetic targets. The term natural product can also
be referred to cosmetics, natural food products and
dietary supplements without any added artificial
ingredients.
In organic chemistry, the definition of natural
products is restricted to purified organic
compounds isolated from natural sources and are
produced as metabolites in primary or secondary
ABSTRACT
Alkaloids are the natural products that are produced during secondary metabolism in living organisms. Alkaloids
are classified into different types. Among them Piperidine and pyrrolidine alkaloids form one of the largest groups
of alkaloids. Piper nigrum (family Piperaceae) is one of the most commonly used spices and considered as ’’The
King of spices’’. It contains major pungent alkaloid Piperine (1-peperoyl piperidine) which is known to possess
many interesting pharmacological actions like antihypertensive, antiplatelets, antioxidant, antitumor,
antiasthmatic, antipyretic, anti-inflammatory, anti-diarrheal, antispasmodic, anxiolytic, hepato-protective,
immuno-modulatory, antibacterial, antifungal, anti-thyroids, antiapoptotic, antimutagenic, anti-spermatogenic,
anti-colon toxin, insecticidal and larvicidal activities etc. Along with the pharmacologically diversified activities,
piperine can also act as bioavailability enhancer.
KEYWORDS
Piperine, Alkaloids, Piper nigrum and Pharmacological activity.
Author for Correspondence:
Suvarna Y,
Department of Pharmaceutical Analysis,
Nirmala College of Pharmacy,
Mangalagiri, Andhra Pradesh, India.
Email: suvarna.ph52@gmail.com
Asian Journal of Research in Chemistry
and
Pharmaceutical Sciences
Journal home page: www.ajrcps.com
Suvarna Y and Abdul Rahaman SK. /Asian Journal of Research in Chemistry and Pharmaceutical Sciences. 7(1), 2019, 293-304.
Available online: www.uptodateresearchpublication.com January – March 294
metabolism
1
. Within the field of medicinal
chemistry, the definition is often further restricted to
secondary metabolites. Secondary metabolites are
not essential for survival, but nevertheless provide
organisms that produce them an evolutionary
advantage. Most of the secondary metabolites that
were selected and optimized through evolution are
used as "chemical warfare" agents i.e. against
competing organisms, prey and predators.
Natural products which have pharmacological or
biological activity can be used for therapeutic
benefits. Therefore, natural products are the active
components of most traditional medicines and in
many modern medicines too. In addition to this, the
structural diversity of natural products can be
achieved by chemical synthesis and so synthetic
analogs are prepared with improved potency and
safety. Natural products are generally considered as
starting points for drug discovery and most of the
drugs approved by U.S. Food and Drug
Administration are inspired from natural products.
Fruits of Piper longum Linn. Commonly called as
black pepper have a long history in Indian
traditional medicine like Ayurveda for treating of
gastro intestinal and respiratory complications
(Johri and Zutshi, 1992). Piperine (1-piperoyl
piperidine) (Meghwal and Goswami, 2013) is an
amide alkaloid extracted from the black pepper
fruits have a number of pharmacological activities
reported such as analgesic, hypertensive, anti-
cancer, neuro protective, anti-inflammatory.
Piperine has also been proved for stimulation of
gastric acid secretion, intestinal lipase and
pancreatic lipase, increased bio-availability and
absorption of other drugs, decreased metabolism by
inhibiting cytochrome 450/CYP 3YP3A4 etc.
Based on the above pharmacological activities it is
demonstrated that piperine has a vast
pharmacological scope for treating several diseases
and also piperine increases the bio-availability and
absorption of different drugs.
BRIEF HISTORY OF ALKALOIDS
Alkaloids are the natural compounds that are
synthesized by the secondary metabolism of living
organisms. These molecules play important roles in
the species that synthesize them but are not essential
for life, unlike products of primary metabolism, e.g.
nucleosides, amino acids, carbohydrates or lipids.
Alkaloids mainly found as carboxylic acid salts of
their nitrogen heterocycles, e.g. citric, lactic, oxalic,
acetic, maleic or tartaric acid salts as well as
fumaric, benzoic, aconitic acid salts. Thus, just as
some plants are noted for containing certain
alkaloids, they may be equally noted for containing
high levels of the particular acid that forms a salt
with the alkaloid. However, because of the polar
and basic nature of alkaloids, most of these occur
dissolved in plant saps as cations, and it is on
evaporation of the sap that the organic acid is
formed. The general physical properties of alkaloids
are colourless, crystalline solids slightly soluble in
neutral or alkaline aqueous solution and readily
soluble in acid or in organic solvents such as ether,
chloroform, or ethanol. Some alkaloids such as
coniine and nicotine are liquid at room temperature,
and few (e.g. sanguinarine) are coloured
2
.
Alkaloids are classified into different types. Among
them Piperidine and pyrrolidine alkaloids form one
of the largest groups of alkaloids known, and as
their name indicates, they include piperidine or
pyrrolidine rings in their structures, which are
derived from the amino acids lysine and ornithine
respectively Figure No.1. These two heterocyclic
structures differ only in carbon-nitrogen skeleton
length, piperidines, have six membered and
pyrrolidines have five membered rings. Irrespective
of the difference in one carbon length, the
biosynthesis of these units is identical, and so the
report mainly points on piperidine alkaloids only,
because it is the main theme throughout the present
project.
PHARMACOGNOSY OF THE PIPER
NIGRUM
Piper nigrum (family Piperaceae) is a valuable
medicinal plant, the most commonly used spices
and regarded as ’’The King of spices’’ among
various spices. Black pepper is mainly cultivated in
many tropical countries like Brazil, India and
Indonesia. Piper nigrum is commonly known as
Kali Mirch in Urdu and Hindi, Pippali in Sanskrit,
Suvarna Y and Abdul Rahaman SK. /Asian Journal of Research in Chemistry and Pharmaceutical Sciences. 7(1), 2019, 293-304.
Available online: www.uptodateresearchpublication.com January – March 295
Milagu in Tamil and Peppercorn, White pepper,
Green pepper, Black pepper, Madagascar pepper in
English. Hot and pungent pepper corns are obtained
from Black pepper which is the most famous and
one of the commonly used spices throughout the
world. Black pepper is used as medicinal agent, as
preservative and in perfumery. Peppercorn of Piper
nigrum or its active constituents are generally used
in different types of foods and as medicine. Pepper
is used in various types of dishes like meat dishes
and also in sauces. It contains Piperine (1-
piperoylpiperidine), major pungent alkaloid Figure
No.2 that shows many pharmacological actions
3
. It
is widely used in different traditional systems of
medicine like Ayurvedic and Unani System of
medicines. Piperine possess diversified
pharmacological activities like antihypertensive,
antioxidant, antitumor, anti-platelets, anti-
asthmatics, anti-inflammatory, antipyretic,
analgesic, antispasmodic, anti-diarrheal,
antidepressant, anxiolytic, hepato-protective,
immuno-modulatory, antibacterial, antifungal, anti-
thyroids, anti-metastatic, antimutagenic,
antiapoptotic, anti-spermatogenic, anti-colon toxin,
insecticidal and larvicidal activities etc. Piperine has
been found to enhance the therapeutic efficacy of
many drugs, vaccines and nutrients by increasing
oral bioavailability by inhibiting various
metabolizing enzymes
4
. It is also found to elevate
fertility and cognitive action. Piperine also found to
stimulate the pancreatic and intestinal enzymes
which aid to digestion. Many therapeutic activities
of this spice are attributed to the presence of
piperine apart from other chemical constituents. The
Piper nigrum fruits are used to produce white and
green peppers. Piper nigrum is also used as a
flavorant.
TAXONOMICAL CLASSIFICATION OF
PIPER NIGRUM
Kingdom: Plantae
Class: Equisetopsida
Sub class: Magnoliidae
Super order: Magnolianae
Order: Piperales
Family: Piperaceae
Genus: Piper
Species: nigrum
PHARMACOGNOSTIC CHARACTERISTICS
Piper nigrum (Black pepper) plant is a woody
perennial climbing flowering vine and belongs to
the family Piperaceae. Pepper plants easily grow in
the shade on supporting trees, trellises or poles up to
maximum height of 13 feet or 4 meters and roots
may come out from leaf nodes if vine touch to the
ground. The plants have heart shapeas long as the
leaves. The spikes length goes up to 7-15 cm. The
fruits of black pepper (drupe) are small with3 to 4
mm in diameter and the dried unripe fruits of Piper
nigrum are called peppercorn. The fully matured
fruits of black pepper are dark red in color and
approximately 5 mm in diameter. A fruit contains a
single seed. The plants starts bearing fruits from
4
th
or 5
th
year, and continues up to seven years. A
single stem contains 20-30 spikes of fruits. The
spikes are collected, sun dried and peppercorns are
separated from the spikes. The fresh unripe green
fruits are harvested and freeze-dried to make green
pepper and some are sun-dried to make black
pepper. From the ripen fruits, red skin is removed
and the seeds are sun-dried to make white pepper.
CHEMICAL COMPOSITION OF PIPER
NIGRUM
The phytochemical investigations of P. nigrum
revealed that it contains variety of phytochemicals.
Piperine was the first pharmacologically active
compound isolated from different members of
Piperaceae family. Various types of compounds like
Phenolics, flavonoids, alkaloids, amides and
steroids, lignans, neolignans, terpenes, chalconesetc
were isolated. Some of the chemical constituents are
Brachyamide B, (2E, 4E)-N-Eicosadienoyl-
pereridine, Guineensine, Dihydro-pipericide, N-
trans-Feruloyltryamine, N-Formylpiperidine,
pentadienoyl as piperidine, (2E, 4E)-
Nisobutyldecadienamide, Tricholein,
Trichostachine, isobutyl-eicosatrienamide, isobutyl-
eicosadienamide, Isobutyl-octadienamide,
Piperamide, Piperine, Piperamine, Piperettine,
Pipericide, Piperolein B, Sarmentine, Sarmentosine,
Suvarna Y and Abdul Rahaman SK. /Asian Journal of Research in Chemistry and Pharmaceutical Sciences. 7(1), 2019, 293-304.
Available online: www.uptodateresearchpublication.com January – March 296
Retrofractamide . The different pharmacological
activities were reported due to the presence of these
phytochemicals. Piperine reported to have four
isomers viz; Piperine, Isopiperine, Chavicine and
Isochavicine (Figure No.3). Among all isolated
compounds isolated from P. nigrum. Piperine,
pipene, piperamide and piperamine were found to
possess diverse pharmacological activities
EVIDENCE BASED PHARMACOLOGICAL
ACTIVITIES
An attempt has been made to collect updated
research information on Piper nigrum from the
internet using Google search engine and Pub Med.
Many researchers carried out their researches on
Piper nigrum and its active constituent ‘’piperine’’
using latest sophisticated scientific technologies and
Important Pharmacological activities of Piper
nigrum and piperine are summarized in Table No.1.
ANTIMICROBIAL ACTIVITY OF BLACK
PEPPER
In 2007, Khan and Siddiqui evaluated the
antibacterial activity of aqueous decoction of Piper
nigrum L. (black pepper), Laurusnobilis L. (bay
leaf), Pimpinella anisum L. (aniseed), and
Coriandrum sativum L. (Coriander) against
different bacterial isolates from oral cavity of two
hundred individual volunteers. Aqueous decoction
Black pepper showed strong antibacterial activity
when compared with aqueous decoction of
Pimpinella anisum and Laurusnobilis at a
concentration of 10μL/disc. In a recent study, the
silver nanoparticles from leaf and stem extract of
Piper nigrum were synthesized and then
antibacterial activity of the synthesized silver
nanoparticles of Piper nigrum was evaluated against
agricultural plant pathogens. These silver nano-
particles showed the excellent antibacterial activity
against plant pathogens. Authors concluded that the
antibacterial activity of silver nano-particles is a
beneficial application in crop improvement and
protection in agricultural nanotechnology
5
.
ANTIOXIDANT ACTIVITY OF BLACK
PEPPER
Free radicals cause many diseases. Various free
radicals that attack on membranes cause oxidation
of lipids, loss of different enzyme activities and
may even cause cancer. Antioxidants completely
stop or delay the process of oxidation. Antioxidant
protection system includes enzymes like Ascorbate,
Catalase, Peroxidase and Superoxide dismutase
which scavenge both radicals and related non
radical oxygen species. Plants are important source
of antioxidants. Some in vitro studies reports that
Piperine inhibits free radicals and reactive oxygen
species, hence possess protective effects against
oxidative damage. Piperine also found to decrease
lipid per oxidation in vivo.
Piper nigrum reported to possess antioxidant
activity that might be due to the presence of
flavonoids and phenolic contents. Piper nigrum was
found to prevent the oxidative stress by inhibiting
lipid per oxidation, human lipoxygenase and
arresting hydroxyl and superoxide free radicals,
decrease lung carcinogenesis in animal studies. The
memory enhancing and antioxidant proprieties of
the methanolic extract of Piper nigrum L. fruits at a
doses of 50 and 100 mg/kg, orally, for 21 days
inamyloid beta (1-42) were investigated in
Alzheimer’s disease model inrats
6-8
. The memory-
enhancing activity of the extract was studied by
means of in vivo (Y-maze and radial arm-maze
tasks) methods. While, the antioxidant activity was
evaluated by measuring activities of glutathione
peroxidase, catalase, superoxide dismutase, and by
measuring the total content of reduced glutathione,
malondialdehyde, and protein carbonyl levels in the
hippocampus. The amyloid beta (1-42)-treated rats
showed the diminishing of spontaneous star
variation percentage within Y- maze task and
enhancement of work memory and reference
memory errors within radial arm-maze task.
Methanolic extract of Piper nigrum showed
significant improvement in memory performance
and showed antioxidant potential on administration.
These studies suggest that methanolic extract of
Piper nigrum ameliorates amyloid beta (1-42)-
induced spatial memory deterioration by depletion
Suvarna Y and Abdul Rahaman SK. /Asian Journal of Research in Chemistry and Pharmaceutical Sciences. 7(1), 2019, 293-304.
Available online: www.uptodateresearchpublication.com January – March 297
of the oxidative stress in the hippocampus of rats.
The antioxidant activity of the three Piper species
(P. nigrum, P. guineense and P. umbellatum) was
studied for the protection of renal, cardiac, and
hepatic antioxidant status in atherogenic diet fed
hamsters. Animals were fed atherogenic diet
addition with different doses of Piper species like P.
nigrum, P. guineense and P. umbellatum at doses of
1 g/kg and 0.25 g/kg for 12 weeks. Piper species
showed significant inhibition of the atherogenic diet
induced increased lipid profile and altered the
antioxidant enzymes activities. This study revealed
an antioxidant role of the extracts of Piper species
against atherogenic diet induced oxidative stress in
renal, hepatic and cardiac tissues.
ANTI-CANCER ACTIVITY OF BLACK
PEPPER
Piper nigrum had been reported to inhibit tumors
formation indifferent experimental models. Many
studied revealed the antitumor activity of P. nigrum
or Piperine by the oral administration. Piperine and
the alcoholic extract of peppercorn showed an
effective antitumor and immunomodulatory
activities. Piperine is also reported to reduce the
lung cancer by altering lipid per oxidation and by
antioxidative protection enzymes activation.
Piperine has distinct pharmacological activities
along with Anti-cancer activity.
Piperine was reported to inhibit G1/S transition and
the proliferation of human umbilical vein
endothelial cells (HUVECs), migration of HUVECs
and in vitro formation of tubule and angiogenesis
induced by collagen and breast cancer cell in chick
embryos. Piperine also inhibits the phosphorylation
of Thr 308 residues of Akt of protein kinase B as
well as Ser 473
9
.
Since phosphorylation of these residues is a
necessary controller of angiogenesis and for proper
functioning of endothelial cells. Therefore, Piperine
may be used as an inhibitor of the angiogenesis for
the treatment of cancer as angiogenesis plays a key
role in the progression of tumor
19
. Docetaxel (a
cytotoxic agent) is an FDA approved drug, used for
the treatment for castration-resistant prostate cancer.
Its metabolism occurs in the liver by hepatic
CYP3A4, and it was revealed that piperine inhibit
the hepatic CYP3A4 enzymatic activity.
Therefore, the administration of docetaxel in
combination with piperine was investigated for both
in vitro and in vivo pharmacokinetic activity of
docetaxel. It was also reported that nutritional use
of piperine increased the efficacy of docetaxel in a
xenograft model devoid of anyside effects on the
mice.
The cytotoxic activity of piperine against many
cancer cell lines was reported earlier. Therefore, the
mechanisms of anticancer activity of piperine
against both androgen independent and dependent
cells of prostate cancer were investigated. The
proliferation of 22RV1, LNCaP, PC-3, and DU-145
prostate cancer cells was found to inhibited by
piperine in dose dependent manner. Piperine
treatment was also found to induce apoptosis, by the
activation of caspase-3 and by the cleavage of
PARP-1 proteins in different prostate cancer cells
like PC-3, DU-145&LNCaP prostate cancer cells.
Treatment with piperine also found to disrupt the
androgen receptor expression in LNCaP prostate
cancer cells and cause significant diminution in the
level of Prostate Specific Antigen in LNCaP cells
10
.
The phosphorylated STAT-3 and Nuclear factor-κB
transcription factors expression were reduced in
LNCaP, DU-145and PC-3prostate cancer cells on
treatment with piperine. These results suggested
that there was a significant reduction in the
androgen dependent and independent growth of
tumor in naked mice model of xeno-transplanted
with prostate cancer cells after treatment of
piperine. Piperine is non-genotoxic and found to
possess anti-mutagenic and anti-tumor influences.
HEPATOPROTECTIVE ACTIVITY OF
BLACK PEPPER
It was found that piperine inhibited the increased
level of serum GPT and GOT in dose-dependent
manner in a hepato-toxicity model of mice caused
by D-galactosamine. The methanolic extract of
Piper nigrum fruits was utilized to evaluate the
hepatoprotective activity in ethanol- CCl4 induced
hepatic damage in Wistar rats. Ethanol-CCl
4
was
used to induce hepatotoxicity in the rats.
Suvarna Y and Abdul Rahaman SK. /Asian Journal of Research in Chemistry and Pharmaceutical Sciences. 7(1), 2019, 293-304.
Available online: www.uptodateresearchpublication.com January – March 298
Prophylactic treatment with methanolic extract of
Piper nigrum at a dose of 100 and 200 mg/kg body
weight, p.o. and piperine at a dose of 50 mg/kg
body weight for pre-treatment, p.o. for 15 days with
Ethanol- CCl
4
treated rats showed significant liver
protection as proved from the triglycerides levels,
Alanine transaminase, Aspartate transaminase,
alkaline phosphatase, bilirubin and superoxide
dismutase, Catalase, Glutathione reductase and
Lipid per oxidation levels to assess the liver
functions. In this study, administration of Ethanol-
CCl
4
exhibited significant boost in triglycerides,
Alanine transaminase, Aspartate transaminase,
alkaline phosphatase, and bilirubin levels while
there was significant decrease in the superoxide
dismutase, catalase, and glutathione reductase levels
which were restored to normal level after pre-
treatment of methanolic extract of Piper nigrum and
Piperine. Lipid per oxidations were also markedly
decreased on pretreatment with the methanolic
extract of Piper nigrum and Piperine at given doses.
The results were close to that of reference standard-
Liv52 at a dose of 1 mL/kg, p.o. treated for 15
days
11
.
The Morphological and histopathological studies of
liver also supported the biochemical parameters.
Thus it is concluded that Piper nigrum possesses
potential hepato-protective activity due to the
presence of piperine alkaloids and have great
therapeutic potential in treatment of liver ailments
ANTI-DIARRHEAL ACTIVITY OF BLACK
PEPPER
Aqueous back pepper extract (ABPE) at a dose of
75, 150, 300mg/kg, po was evaluated for anti-
diarrheal, anti-motility and anti-secretory activity in
mice
12
. The castor oil and magnesium sulphate were
used to induce diarrhea for the evaluation of anti-
diarrheal activity and gastrointestinal motility was
assessed by charcoal meal, while castor oil was
used for the evaluation of anti-motility and anti-
secretory activities.
ABPE showed a significant and dose dependent
anti-diarrheal, anti-motility and anti-secretary
effect. Anti-motility and anti-secretory activities of
Piper nigrum might be due to the presence of
carbohydrates and alkaloids, and anti-diarrheal
activity of ABPE may be due to its anti-motility and
anti-secretory activities.
IMMUNO-MODULATORY ACTIVITY OF
BLACK PEPPER
Piperine at a concentration of 250μg/mL was
reported to be cytotoxic to Dalton’s lymphoma
ascites and Ehrlich as cites carcinoma cells.
Piperine of 50μg/mL concentration showed
cytotoxic activity on L929 cells in culture. Piperine
administration also causes an increase in the total
WBC counts in Balb/c mice. On administrations of
piperine there was an increase the bone marrow
cellularity and alpha-esterase positive cells
In vitro immunomodulatory activity of piperine was
evaluated to enhance the efficacy of rifampicin in a
murine model of Mycobacterium tuberculosis
infection. Mouse splenocytes were used to evaluate
in-vitro immune modulation of piperine for
cytokine production, macrophage activation and
lymphocyte proliferation. Mouse splenocytes when
treated with piperine showed an increase in the Th-1
cytokines (IFN-γ and IL-2) secretion, increased
macrophage activation and proliferation of T and B
cell. Protective efficacy of piperine and rifampicin
(1 mg/kg) combination against Mycobacterium
tuberculosis was reported due to immuno-
modulatory activity
13
.
DIGESTIVE ACTIVITY OF BLACK PEPPER
Many spices are known for their digestive stimulant
action. Dietary piperine enhances digestion by
stimulation of the pancreatic enzymes and
considerably decreases the food transit time of
gastrointestinal tract. Piperine has been reported to
increases the saliva production and gastric
secretions, and increases the production and
activation of salivary amylase
14
.
ANTI-CONVULSANT ACTIVITY OF BLACK
PEPPER
The oral administration of Piperine or P. nigrum
showed a delayed onset of myoclonic jerks and
generalized clonic at 40 and 80mg/kg doses and
Piperine also diminishes the seizure stage and
Suvarna Y and Abdul Rahaman SK. /Asian Journal of Research in Chemistry and Pharmaceutical Sciences. 7(1), 2019, 293-304.
Available online: www.uptodateresearchpublication.com January – March 299
mortality when compared with vehicle treated
animals. A significant reduction was also observed
in the incidence of MES-induced tonic hind limb
extension (THE) and PTZ-induced Fos immune
reactivity in the dentate gyrus after of piperine
administration. Capsazepine, a TRPV1-selective
antagonist blocked the anti-convulsant effects of
piperine. These data reveals the anti-convulsant
activity of piperine. An alternative study was done
to evaluate in vivo anticonvulsant activity of
piperine was in pentylenetetrazole (PTZ) and
picrotoxin (PIC)-induced seizures models of
epilepsy in mice. A significant (P<0.01) delayed in
the onset of PTZ-and PIC-induced seizures was
observed after intra-peritoneal injection of piperine
at a dose of 30, 50 and 70 mg/kg (i.p.), valproic acid
at a dose of 200 mg/kg, Carbamazepine at a dose of
30 mg/kg and diazepam at a dose of 1 mg/kg in
mice. These results revealed the anti convulsant
effects of piperine which possibly mediated via
GABA ergic Pathways
15
. In another study, in vivo
anticonvulsant activity of piperine was evaluated
inpentylenetetrazole (PTZ) and picrotoxin (PIC)
induced seizures models of epilepsy in mice.
ANTIDEPRESSANT ACTIVITY OF BLACK
PEPPER
The antidepressant-like effect of piperine and its
possible mechanisms were evaluated in
corticosterone-induced model of depression in
mice
16
. Depression-like response was developed in
mice after 3 weeks of corticosterone injections. The
depression was revealed by the significant reduction
in sucrose utilization and augmentation in
immobility time in the forced swim test and tail
suspension test. Further, the brain-derived
neurotropic factor protein and mRNA levels in the
hippocampus were also significantly decreased in
corticosterone-treated mice. Corticosterone induced
the behavioral and biochemical changes were
significantly diminished after treatment to animals
with Piperine. These results showed that piperine
produces an antidepressant-like effect in
corticosterone-induced model of depression in mice.
Piperine produces an antidepressant-like effect in
corticosterone-induced model of depression in mice
mediated via GABA ergic pathways.
CYTOTOXIC ACTIVITY
Duh CY et al, reported cytotoxic activity of
chloroform extracts of Piper aborescens leaves.
Cyclobutanoid amides with trans-trans-trans
configurations such as piperarborenine C,
piperarborenine D and piperarborenine E and new
furanoid lignan, (+) arborone, along with twelve
known compounds were isolated from the stems of
Piper arborescens. The structures of these new
compounds were determined by means of spectral
analysis. Piperarborenines A-E, aristolactam BIII,
goniothalactam showed significant cytotoxic
activity against P-388, HT-29 and A549 cell lines in
vitro
17
. Tang GH et al, reported the cytotoxic
activity of amide alkaloid which was obtained from
methanolic extract of Piper boehmeriaefolium
18
.
Pan L et al, reported cytotoxic activity of
chloroform extract of Piper sermentosum
19
.
ANTIPLATELET ACTIVITY
Lei D et al, reported antiplatelet activity of aqueous
extract of inflorescence Piper betle, where
inflorescence Piper betle inhibited the arachidonic
acid induced and collagen-induced platelet
aggregation
20
. Li CY et al, also mentioned that the
methanolic extract of Piper lolot showed potent
inhibitory activity on platelet aggregation.
CYP3A4 INHIBITORY EFFECT
Usia T, Watabe T, Kadota S, et al, mentioned the
potent inhibitory activity of aqueous extract of
Piper cubeba on the metabolism mediated by
CYP3A4 enzyme. Human liver microsome was
used for CYP inhibitory assay. The inhibitory
activity on the metabolism mediated by CYP3A4 in
vitro was determined using a radiometric
measurement
21
.
ANTI-INFLAMMATORY ACTIVITY
Lin LC et al, mentioned anti-inflammatory activity
of methanolic extract of Piper kadsura stem.
Among the constituents that were isolated from the
stems of Piper kadsura futoquinol, piperlactam S,
Suvarna Y and Abdul Rahaman SK. /Asian Journal of Research in Chemistry and Pharmaceutical Sciences. 7(1), 2019, 293-304.
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and N-p-coumaroyl tyramine showed potent
inhibition of PMA-induced ROS production in
human polymorphonuclear neutrophils
22
.
ANTI-PLASMODIAL ACTIVITY
Flores N et al, reported anti plasmodial activity
against Plasmodium falciparum of ethanolic extract
of Piper glabratum leaves. Among the evaluated
compounds, methyl-3,4-dihydroxy-5-(3'-methyl-2'-
butenyl) benzoate exhibited leishmanicidal effect
(IC50 13.8-18.5 µ g/mL) against the three
Leishmania strains used, and methyl 3,4-dihydroxy-
5-(2-hydroxy-3-methylbutenyl)benzoate, methyl 4-
hydroxy-3-(2-hydroxy-3-methyl-3-
butenyl)benzoate, and methyl 3,4-dihydroxy-5-(3-
methyl-2-butenyl) benzoate showed significant
trypanocidal activity
23
.
ANT-REPELLENT ACTIVITY
Capron M A et al, reported ant repellent activity of
chloroform fraction of hexane extract of Piper
tuberculatum leaves. Green TP et al. also reported
ant repellent activity of leaves
24
.
ANTIFUNGAL ACTIVITY
The essential oil of the fruits of P. longum L
exhibits fungicidal activity
25
. The substances
derived from fruit was tested against six
phytopathogenic fungi, Pyricularia oryzae,
Rhizoctonia solani, Botrytis cineria, Phytophthora
infestans, Puccini are condita, and Erysiphe
graminis using a whole plant in vivo method.
Pipernonaline, a piperidine alkaloid was isolated
from the hexane fraction of P. longum showed a
potent fungicidal activity against P. recondita at the
concentration of 0.5 and 0.25 mg /ml, with 91% and
80% control values respectively.
ANTI-ASTHMATIC ACTIVITY
An extract of the fruits in milk reduced passive
cutaneous anaphylaxis in rats and protected guinea
pigs against antigen-induced bronchospasm
26
.
ANTI-DIABETIC ACTIVITY
The antihyperglycemic and anti-lipid per oxidative
effects of ethanolic extract of Piper longum dried
fruits in alloxan induced diabetic rats were studied.
The blood glucose level, carbohydrate metabolizing
enzymes and the status of lipid per oxidation and
antioxidants were assayed using specific
colorimetric methods. Oral administration of dried
fruits has shown significant anti-hyperglycemic,
antilipid per oxidative and antioxidant effects in
diabetic rats comparable to that of the standard
reference drug glibenclamide
27
.
HYPOCHOLESTEROLAEMIC ACTIVITY
Methyl piperine significantly inhibited the elevation
of total serum cholesterol, and the total cholesterol
to HDL cholesterol ratio, in rats fed with a high
cholesterol diet. The unsaponificable fraction of the
oil of P. longum also significantly decreased total
serum cholesterol and hepatic cholesterol in
hypercholesterolaemic mice
28
.
ANTIULCER ACTIVITY
The aqueous extract of ginger, one of the
constituents of Mahakasyaya drugs along with
aqueous extract of P. longum and also the colloidal
solution of Ferula asafoetida were reported to
protect against CRS-ASP and PL- induced gastric
ulcers in rats. Piperine, an alkaloid of long peppers,
inhibited gastric emptying (GE) of solids/liquids in
rats and gastrointestinal transit (GT) in mice in a
dose and time dependent manner. GE inhibitory
activity of piperine is independent of gastric acid
and pepsin secretion
29
.
ANALGESIC ACTIVITY
Roots of P. longum was evaluated for opioid type
analgesia using rat tail-flick method as well as for
NSAID type analgesia using acetic-acid writhing
method by using pentazocine and ibuprofen as drug
controls
30
. An aqueous suspension of root powder
of P. longum was administered orally to rat and
mice. The study revealed that P. longum root shows
weak opioid and potent NSAID type of analgesic
effect.
Suvarna Y and Abdul Rahaman SK. /Asian Journal of Research in Chemistry and Pharmaceutical Sciences. 7(1), 2019, 293-304.
Available online: www.uptodateresearchpublication.com January – March 301
Table No.1:
Pharmacological Activities
S.No PHARMACOLOGICAL ACTIVITIES
1 Anti-hypertensive
2 Anti-asthmatic
3 Cognitive action & fertility activity
4 Anti-microbial
5 Anti-oxidant
6 Anti-cancer
7 Anti-inflammatory
8 Hepatoprotective
9 Anti-diarrheal activity
10 Digestive activity
11 Antidepressant activity
12 Immunomodulatory activity
13 Anticonvulsant activity
14 Analgesic activity
15 Effect of piperine on metabolism
Figure No.1: Biosynthesis of Piperidine alkaloids
Figure No.2: Structure of Piperine
Suvarna Y and Abdul Rahaman SK. /Asian Journal of Research in Chemistry and Pharmaceutical Sciences. 7(1), 2019, 293-304.
Available online: www.uptodateresearchpublication.com January – March 302
Figure No.3: Isomers of Piperine
CONCLUSION
Natural products are used as medicines for many
years and they are the main sources of drugs for
many treatments. Drugs obtained from natural
sources are efficacious with fewer side effects when
compared with synthetic drugs. Black pepper, the
king of spices has piperine alkaloid as a major
chemical constituent and it is showing wide range
of pharmacological activities which raises the
importance of black pepper and a preferable one for
regular intake with food. Piperine formulations are
available in market for treating different disease
conditions and also piperine is used in combination
with other drugs to enhance the bioavailability.
ACKNOWLEDGEMENT
The authors wish to express their sincere gratitude
to Department of Pharmaceutical Analysis, Nirmala
College of Pharmacy, Mangalagiri, Andhra Pradesh,
India for providing necessary facilities to carry out
this review work.
CONFLICT OF INTEREST
We declare that we have no conflict of interest.
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Please cite this article in press as: Suvarna Y and Abdul Rahaman SK. Pharmacotherapeutic properties of black
pepper: a systematic review, Asian Journal of Research in Chemistry and Pharmaceutical Sciences, 7(1), 2019, 293-
304.
